ObjectiveWe assessed vaccine effectiveness (VE) of BNT162b2 mRNA COVID-19 vaccine against SARS-CoV-2 acquisition among health care workers (HCWs) of long-term care facilities (LTCFs).MethodsThis prospective study, in the framework of "Senior Shield" program in Israel, included routine, weekly nasopharyngeal SARS-CoV-2 RT-PCR testing from all LTCF HCWs since July 2020. All residents and 75% of HCWs were immunized between December 2020 and January 2021. The analysis was limited to HCWs adhering to routine testing. Fully vaccinated (14+ days after second dose; n=6960) and unvaccinated HCWs (n=2202) were simultaneously followed until SARS-CoV-2 acquisition, or end of follow-up, April 11, 2021. Hazard ratios (HRs) for vaccination vs. no vaccination were calculated (Cox proportional hazards regression models, adjusting for socio-demographics and residential-area COVID-19 incidence). VE was calculated as [(1– HR)×100]. RT-PCR cycle threshold values (Cts) were compared between vaccinated and unvaccinated HCWs.ResultsAt >14 days post second dose, 40 vaccinated HCWs acquired SARS-CoV-2 (median follow-up, 66 days; cumulative incidence 0.6%) vs. 84 unvaccinated HCWs (median follow-up 43 days; cumulative incidence, 5.1%); HR=0.11 (95% CI 0.07, 0.17), unadjusted VE=89% (95% CI 83%, 93%). Adjusted VE beyond seven days and >14 days post second dose were similar. The median PCR Cts targeting ORF1ab gene among 20 vaccinated and 40 unvaccinated HCWs was 32.0 vs. 26.7, respectively, p=0.008.ConclusionsVE following two doses of BNT162b2 against SARS-CoV-2 acquisition in LTCF HCWs was high. The lower viral loads among SARS-CoV-2 positive HCWs suggests further reduction in transmission.